tbuckley/cabot-search huggingface dataset:
Abstract 11381: Associations Between Serum and Dietary Omega-3 to Omega-6 Ratio and Cognitive Function in a Population of Community-Dwelling Japanese. -Tanushimaru Study-
Authors: Ako Fukami, Hisashi Adachi, Mika Enomoto, Yume Nohara, Morikawa Nagisa, Akiko Sakaue, Yamamoto Maki, Hiromi Sato, Yoshihiro Fukumoto
Journal: Circulation (2022)

Introduction: Previous studies indicate that dietary omega-3 polyunsaturated fatty acids (PUFA) are modifiable risk factors for CVD and cognitive decline. This study aimed to investigate the association between serum and dietary omega-3/omega-6 PUFA ratio and cognitive function were measured in a general population. Hypothesis: We assessed the hypothesis that the serum and dietary omega-3/omega-6 PUFA ratio preserve a cognitive function. Method: A total of 976 residents (381 males, 595 females, mean age 62.6 years) underwent a physical examination, a nutrition survey and the mini-mental state examination as an evaluation of cognitive function in 2009 and followed up in 2018. Results: The serum omega-3/omega-6 ratio were significantly associated with age (p &amp;lt; 0.0001), sex (male, p &amp;lt;0.0001), MMSE ( p &amp;lt; 0.0001), LDL-c ( inversely, p &amp;lt; 0.01), and salt intake ( p &amp;lt; 0.05), using by multiple stepwise regression analysis. The dietary intake of proteins from fish ( p &amp;lt; 0.0001), trace elements, ( p &amp;lt; 0.01), vitamin D, B6, B12 ( p &amp;lt;0.0001), and salt ( p &amp;lt; 0.0001) showed dose dependent relationships with the serum omega-3/omega-6 ratio using analysis of covariance. Subjects were divided into 4 groups according to their progression of cognitive decline in 10 years. Serum omega-3/omega-6 ratio of group with normal cognitive function (NC) were significantly higher than those of group with cognitive decline (CD) (p &amp;lt; 0.05). However, dietary intakes of omega-3 and omega-6 PUFA were not significant. Interestingly, salt intakes in group with CD were higher than those in group with NC (p &amp;lt; 0.05). The logistic regression analysis revealed that salt intakes was associated with cognitive decline 10 years later after adjustments for confounding factors (odds ratio, 1.1; 95% C.I., 1.01-1.13; p = 0.01) In conclusion, the present study demonstrated that omega-3 PUFA may preserve a cognitive function and excessive intakes of salt may have an adverse effect on cognitive function.
Abstract 11548: Gender Disparities After Transcatheter Aortic Valve Replacement With Newer Generation Transcatheter Heart Valves: A Systematic Review and Meta-Analysis
Authors: Angkawipa Trongtorsak, Sittinun Thangjui, Pabitra Adhikari, Biraj Shrestha, Jakrin Kewcharoen, Leenhapong Navaravong, Somsupha Kanjanauthai, Steve Attanasio, Hammad A saudye
Journal: Circulation (2022)

Background: Evidence demonstrated gender disparities after transcatheter aortic valve replacement (TAVR) with early generation transcatheter heart valves (THV)s. However, it is unclear whether gender-related differences persist with the newer generation THVs. We conducted this meta-analysis and systematic review to assess gender disparities after TAVR with newer generation THVs Methods: We searched MEDLINE, and Embase databases from inception to May 2022 to identify studies that reported gender-specific outcomes after TAVR with newer generation THVs (Sapien 3, Corevalve Evolut R, and Evolut Pro). Outcomes of interests included 30-day mortality, 1-year mortality and vascular complications. Data were pooled using random-effects models to calculate pooled odds ratio (OR) and 95% conference interval (CI). Results: Four studies with a total of 47,933 patients (21,073 in females and 26,860 in males) were included. Ninety-six percent received TAVR via transfemoral approach. Females had higher 30-day mortality (OR = 1.53, 95%CI 1.31-1.79, p-value (p) &lt; 0.001) and vascular complications (OR=1.43, 95%CI 1.23-1.65, p&lt; 0.001). However, 1-year mortality was similar between 2 groups (OR=0.83, 95%CI 0.67-1.04, p=0.33). Conclusions: Higher 30-day mortality after TAVR in females may be attributed from higher vascular complications. Further research is needed to explore potential causes of increased mortality. While vascular complications may be an etiology, other patient characteristics or procedure-related issues should be evaluated.
Abstract 11180: Assessing the Impact of the Covid-19 Pandemic Shelter in Place on Glycemic Control and Blood Pressure in Diabetic Patients
Authors: Akshay Bommireddi, Maqdooda Merchant, Jennifer Huynh, Amie Cai, Kyle Yamamoto, joseph Vu, Seema Pursnani
Journal: Circulation (2022)

Introduction: The impact of the COVID-19 pandemic state and county orders for home isolation and social distancing on glycemic control in diabetics is yet to be understood. We aimed to evaluate the impact of California’s 2019 shelter-in-place (SiP) order (mandated from March to June 2020) on glycemic control, blood pressure, and body mass index in the Kaiser Permanente Northern California (KPNC) diabetic population. Methods: This is a retrospective cohort study of Kaiser Permanente Northern California members, age ≥ 18 years old with a diagnosis of type 1 or type 2 diabetes prior to 2019. We evaluated the change in glycated hemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), use of oral hypoglycemic agent (OHA), and use of insulin for diabetics, stratified by pre-SiP HbA1c level (&lt;7, 7-8, 8-9, 9-10, and &gt;10%) prior to and following the SiP order. Results: A total of 168,621 diabetics were included. Prior to the SiP, the mean HbA1c was 7.45 (1.48)%, with a mean BMI of 31.81 (7.29), SBP 133.04 (13.84), DBP 70.79 (9.97), 72.06% OHA users and 28.64% insulin users. Following SiP, the mean HbA1c was 7.49 (1.57)%, BMI 31.51 (7.39), SBP 134.12 (15.68) and DBP 71.30 (10.52), and 72.41% OHA users and 29.25% insulin users. A marginal decrease in BMI, was seen across all groups. Increases in HbA1c, SBP, DBP were highest in the HbA1c&lt;7% and 7-8% groups (p&lt;0.0001, Table 1). Conclusions: Marginal increases in HbA1c, SBP and DBP were seen in this diabetic cohort following the California 2020 SiP order. Increased use of OHA and insulin were seen following SiP, with insulin initiation in the highest HbA1c groups. The study helps to identify diabetics in our Northern California cohort that require more intensive management in the post-pandemic era. Further studies will help characterize long-term impacts on risk factors and incident cardiovascular disease.
Abstract 12647: Acute Glucocorticoid Receptor Activation Induces Rat Heart Cardioprotection Against Infarction Through Na+/h+ Exchanger Regulation
Authors: Daiana S Escudero, Juliana C Fantinelli, Maria E Amarillo, Nestor G Perez, Romina G Diaz
Journal: Circulation (2022)

Introduction: Acute corticosteroid therapy has been used in the prophylaxis against atrial fibrillation following cardiac surgery or acute myocardial infarction (AMI). Glucocorticoid (GR) and mineralocorticoid (MR) receptors are highly expressed in cardiac tissue. While MR activation during AMI was linked to Na + /H + exchanger (NHE1) activation-mediated increase in infarct size and contractile dysfunction, lesser is known about GR effects. The aim of this work is to seek the functional effects of an acute dose of a low potency corticosteroid (hydrocortisone, HC) in a rat model of AMI. Methods: AMI was promoted in isolated hearts from Wistar rats by 40min of regional ischemia followed by 60min reperfusion (ischemic control “I”, n=4). 10nM HC (HC10, n=3) or HC10 plus the GR inhibitor Mifepristone (M, 10uM, n=5) was added to the perfusate during the first 10min of reperfusion. In isolated papillary muscles from non-infarcted hearts NHE1 activity was measure by analyzing the pH recovery from an acute transient acidosis (TA) in control conditions, and in the presence of HC 1nM (HC1) or HC10. Protein phosphorylation and expression were determined by western blot. Data are expressed as mean±S.E.M. Results: HC treatment reduced infarct size (% of risk area: 38±3 I; 9±3 HC10, p&lt;0.05, t-test), improved left ventricular developed pressure, LVDP (% of preischemic control: 28±4 I vs. 60±5 HC10, P&lt;0.05, t-test) and decreased left ventricular end diastolic pressure, LVEDP (in mmHg: 55±4 I vs. 28±5 HC, P&lt;0.05, t-test). M avoided HC protective effects (infarct size 24±4%; LVDP 34±10%; LVEDP 10±2 mmHg). HC reduced NHE1 activity (JH+ in mmol/ml/min: 1.22±0.19 TA, n=5; 0.68±0.11 HC1, n=4; 0.56±0.15 HC10, n=4, p&lt;0.05, ANOVA). Neither NHE1 expression nor the NHE1 pro-activating Ser703 phosphorylation were modified. HC10 increased NHE1 pro-inhibiting Ser648 phosphorylation (% of control: 102±7 TA, 111±16 HC1, 155±23 HC10, n=8, p&lt;0.05, ANOVA). In line, AKT phosphorylation level was increased by HC (% of control: 102±18 TA, 160±20 HC1, 202±24 HC10; n=9, p&lt;0.05, ANOVA). Conclusions: Our results show that HC induce cardiac protection against AMI via GR activation, through a mechanism that may be assigned to an inhibitory AKT-mediated Ser648 NHE1 phosphorylation.
Abstract 12169: Re-Imagining Fontan Support: Novel Cavopulmonary Connection Can Accommodate Mechanical Circulatory Support, Augment Cardiac Output and Balance Hepatic Flow
Authors: Priyanka Hardikar, Vincent Cleveland, Jacqueline Contento, Paige Mass, Qiyuan Wu, Yue-Hin Loke, Axel Krieger, Pranava Sinha, Laura Olivieri
Journal: Circulation (2022)

Introduction: Improved Fontan survivorship requires novel treatments for late complications and inevitable failure. Typical total cavopulmonary connection (TCPC) shapes perform well in the short term yet competitive flows create challenges in providing mechanical circulatory support (MCS) due to two inflows/outflows. A novel, feasible Fontan shape, the Convergent Cavopulmonary Connection (CCPC), converges venous return to create a single inflow and outflow for easy institution of MCS, and maintains favorable hepatic flow distribution (HFD) and power loss. The impact of MCS on CCPC hemodynamic performance is still unknown. Hypothesis: In vitro implantation of a single MCS device into patient-specific CCPCs will be feasible and produce augmented cardiac output and acceptable HFD, compared to traditional TCPC. Methods: A benchtop mock circulatory flow loop using 60/40 glycerin equipped with inlet/outlet flow meters and outflow optical registers was used to analyze five 3D-printed TCPC and CCPC models derived from cardiac MRI images. Patient-specific flow conditions were applied to each model’s inlets/outlets. HFD was measured using an injection of blue tracer dye in the IVC and the optical concentration at the LPA and RPA outlets was compared. The CCPC models were also retrofitted to accommodate an Impella ventricular assist device (VAD) and PediPump VAD. HFD and cardiac index (CI) (IVC+SVC flow return) were compared with linear regression and paired t-test. Results: All CCPC HFD were within optimal range. Addition of either MCS device to the CCPC creates incremental increase of CI (p&lt;0.01) and significant improvement in HFD balance vs baseline TCPC (p=0.03), reflecting the dominance of the MCS mixing over anatomic influence on HFD. Conclusions: Patient-specific CCPC Fontan designs can successfully accommodate MCS implantation. Addition of MCS in benchtop testing shows improved CI and HFD, mitigating anatomic impact on HFD.
Abstract 12575: Subgroup Comparison of Deep-Learning Electrocardiogram Model Performance for Predicting New-Onset 1-Year Atrial Fibrillation Incidence
Authors: Hakje Yoo, Yunjin Yum, Jong-ho Kim, Hyung Joon J Joo
Journal: Circulation (2022)

Background: Surveillance of high-risk individuals as determined by an atrial fibrillation (AF) prediction model would be a good strategy to prevent stroke and other complications from AF. Recently, several deep learning (DL) models to predict new onset AF using 12-lead electrocardiography (ECG) have been introduced. However, their performance has not been compared among different patient groups. Methods : Data of 99,281 patients who underwent 12-lead ECG at Korea University Anam Hospital from January 2017 to December 2019, excluding patients already diagnosed with AF, were studied. The data was split into a 60% training set, 20% validation set and 20% test set. Using age, sex, and raw ECG waveforms as inputs, DL models of ResNet and a multi-layered perceptron module were developed to predict 1-year new onset AF incidence. Results: The DL model using both ECG waves and simple demographic information (age and sex) as input (ECG-AS model) showed better performance compared to the DL model using only ECG waves (ECG model) for AF prediction in the test dataset (area under the receiver operating characteristics curves [AUROCs] 0.79 for ECG model and 0.89 for ECG-AS model, respectively). In subgroup analysis divided by clinical features such as CHA2DS2-VASC score, there was little difference in the performance of the DL model. Interestingly, The DL model performed worse in patients with normal sinus rhythm (NSR) compared to patients with non-NSR (AUROC 0.70 vs 0.81 for ECG model, 0.82 vs 0.90 for ECG-AS model, Table 1). Conclusions: ECG of NSR may not have sufficient information to predict AF. In applying the AF prediction DL model using 12-lead ECG to real-world clinical practice, it may be helpful to add clinical information to the input along with appropriate patient selection.
Abstract 12619: Diverse Effects of Cilostazol on Proprotein Convertase Subtilisin/Kexin Type 9, Obesity or Not
Authors: Po-Wei Chen, Shih-Ya Tseng, Ting-Hsing Chao
Journal: Circulation (2022)

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis. Cilostazol exerts favorable cellular and metabolic effects; however, the effect of cilostazol on the expression of PCSK9 has not been previously reported. Hypothesis: Our study aimed to investigate the potential mechanisms of action of cilostazol on the expression of PCSK9 and lipid homeostasis. Methods: We evaluated the effects of cilostazol on the expression of PCSK9 in HepG2 cells and evaluated potential molecular mechanisms by measuring signaling molecules in the liver and serum lipid profiles in high-fat diet-induced obese mice and normal chow-fed mice. Additionally, the baseline and post-treatment serum PCSK9 levels of obese and non-obese human participants treated with cilostazol were measured. Results: Cilostazol treatment significantly induced the messenger RNA and protein expression of PCSK9 in HepG2 cells and enhanced PCSK9 promoter activity. Chromatin immunoprecipitation assays confirmed that cilostazol treatment enhanced PCSK9 transcription by binding to peroxisome proliferator-activated receptor-γ (PPARγ) via the PPARγ DNA response element. PPARγ knockdown attenuated the stimulatory effect of cilostazol on PCSK9. In vivo experiments revealed that cilostazol treatment increased serum levels of PCSK9 in normal mice but significantly reduced PCSK9 levels in obese mice (Figure). Clinical data showed that cilostazol treatment significantly reduced serum PCSK9 levels in patients with obesity. The expressions of relevant miRNAs also showed consistent results. Conclusions: The obesity-dependent effects of cilostazol on PCSK9 expression observed from bench to bedside demonstrate the therapeutic potential of cilostazol in clinical settings.
Abstract 11488: Comparative Effectiveness of PET and SPECT Myocardial Perfusion Imaging for Identification of Low-Risk Patients With Cardiometabolic Disease
Authors: Daniel M Huck, Brittany N Weber, Sanjay Divakaran, Jenifer M Brown, Diana M Lopez, Ana Carolina do A. H. de Souza, Shelby Laychak, Jon Hainer, Ron Blankstein, Sharmila Dorbala, Marcelo F Di Carli
Journal: Circulation (2022)

Introduction: The epidemiology of coronary artery disease (CAD) has shifted, with increasing cardiometabolic (CM) disease and decreasing obstructive CAD in patients referred for myocardial perfusion imaging (MPI). Coronary microvascular dysfunction, defined as impaired coronary flow reserve (CFR) by positron emission tomography (PET), has emerged as a key mediator of risk. Our objective was to assess whether CFR provides additive value to identify low-risk CM disease patients compared with single-photon emission computed tomography (SPECT) MPI. Methods: We retrospectively studied patients with CM disease (obesity, diabetes, or chronic kidney disease (CKD) stage ≥3) and without known CAD referred for PET or SPECT MPI at our center from 2006 to 2020. Annualized all-cause and cardiac mortality was determined from death certificates, and propensity-matched low-risk PET and SPECT patients were compared using Poisson and Cox regression. Results: CM disease was prevalent in consecutive MPI referrals without CAD including obesity (N=8869), diabetes (N=4896) and CKD (N=3555), and higher among PET MPI (p &lt;0.001). Prevalence of summed stress score (SSS) &gt;3 reflecting obstructive CAD was low (12%, 15% and 16%). Conversely, prevalence of CFR &lt;2 was high (52%, 61% and 69%), reflecting impaired myocardial perfusion. In adjusted hazard analysis, normal MPI was associated with lower risk of all-cause and cardiac death (p &lt;0.001). Normal PET (SSS ≤3 and CFR &gt;2) was associated with lower all-cause death compared to normal SPECT (Figure, A). Normal PET and SPECT identified low-risk (&lt;1%/year cardiac death) patients with obesity and diabetes, however those with CKD remained moderate-risk (1-3%/year) (Figure, B). Conclusion: CM disease is common among patients without CAD referred for MPI. Normal PET and SPECT MPI identify a low-risk group for obesity and diabetes, but not CKD. PET with CFR has additive prognostic utility to identify low-risk individuals compared to SPECT.
Abstract 12631: Phenome-Wide Prediction of Incident Circulatory Diseases Using Machine Learning-Derived Features From Retinal Imaging
Authors: Seyedeh Zekavat, Saman Doroodgar, Vineet Raghu, Sayuri Sekimitsu, Elizabeth Rossin, Janey Wiggs, Puneet Batra, Marzyeh Ghassemi, Nazlee Zebardast, Pradeep Natarajan
Journal: Circulation (2022)

Purpose: The retina is a window for assessment of cardiovascular health. Here, we performed machine learning-based assessment of retinal vascular density (RVD) from fundus photos, and combined this with retinal layer thicknesses from optical coherence tomography (OCT) imaging, to predict incident circulatory conditions. Methods: We utilized UK Biobank participant retinal fundus images (N=54,813), and OCT images (N=44,823). Deep-learning of fundus photos was used to remove poor-quality images and segment the retinal microvasculature to calculate RVD. Using the Topcon Segmentation algorithm, we quantified retinal layer thicknesses. We performed Cox survival analyses, separately associating RVD and retinal layer thicknesses with 130 circulatory conditions from Phecode ICD-9 and ICD-10 composite phenotypes (median 10 year follow-up), adjusting for age, sex, smoking, ethnicity, height, weight, and spherical equivalent. False Discovery Rate (FDR&lt;0.05) correction was performed to identify significant associations. Results: Participants’ mean age was 56 (SD 8 years), 55% were female, and 56% were non-smokers. Associations were observed for each SD of photoreceptor thinning with incident abdominal aortic aneurysms (HR 1.47, P=6e-6), peripheral vascular disease (HR 1.32, P=4e-5), nonhypertensive heart failure (HR 1.20, P=2.8e-6), myocardial infarction (HR 1.17, P=8e-7), cerebrovascular disease (HR 1.15, P=1.9e-5) and hypertension (HTN) (HR 1.09, P=1e-12). Each SD of lower RVD was associated with incident HTN (HR 1.15, P=3.8e-39) and hypertensive heart disease (HR 2.07, P=6e-4). Further incident heart failure analysis additionally adjusting for RVD, prevalent HTN, and type 2 diabetes identified a persistent association for photoreceptor thinning. Conclusions: Our results indicate that photoreceptor thinning and RVD from retinal imaging can serve as a biomarker for future cardiovascular conditions, independent of other common risk factors.
Abstract 12390: Accelerometer-Based Digital Measurement of Functional Capacity in Heart Failure Patients
Authors: Felis Dwiyasa, Prashant Vaishnava, Christopher J McLeod, Sandi Wibowo, Jackie Velarde, David K Sim, Dinna Kar Nee Soon, Raymond C Wong, Shao Guang Sheldon Lee, Seet Yoong Loh, Hao Chen, Maulik Majmudar
Journal: Circulation (2022)

Introduction: Repeated 6MWT in clinic are inconvenient for patients and disruptive to usual clinic throughput. Digital measures may be a means to overcome these challenges and reliably measure functional capacity. Methods: As part of an observational clinical trial (NCT04191356), during an 8-week observation period, patients with heart failure (HF) utilize arm-band biosensors (Biofourmis Everion®) for at least 15 hours daily while carrying out daily activities and complete an in-clinic investigator-guided 6MWT on the first and last days of participation. Interim data (N=30, age 56.17 ± 11.26; 24 males; 3 NYHA I, 25 NYHA II, 2 NYHA III) are used for validation, where the distance of baseline 6MWT is used as reference standard. Results: Passive 6MWT, which is the maximum 6-minute step count derived from daily accelerometer data (Fig 1), is strongly correlated with the reference standard (R=0.7501, P&lt;0.0001, N=30) (Fig 2). Further analysis (Fig 2) reveals that regardless of the duration of the step count, the digital measures consistently have strong correlations with the reference standard, with the highest correlation obtained by Passive 10MWT (R=0.7746, P&lt;0.0001, N=30). Conclusions: Early data highlights that accelerometer data collected during daily activities appears to indicate functional capacity of HF patients. Continued data will validate digital measures against various patient outcomes. Fig 1 Aggregation of Passive 6MWT from step count recorded during daily activities Fig 2 Correlation between accelerometer-derived passive step count digital measures and distance manually measured during baseline investigator-guided 6MWT as reference standard (N=30)
Abstract 12010: Efficacy and Safety of Dofetilide and Sotalol in Patients With Hypertrophic Cardiomyopathy
Authors: Christopher R Chen, Mallika Lal, Yunwoo Burton, Hongya Chen, Eric Stecker, Ahmad Masri, Babak Nazer
Journal: Circulation (2022)

Introduction: Patients with hypertrophic cardiomyopathy (HCM) often have atrial fibrillation (AF) and ventricular arrhythmias (VA) requiring rhythm control. In the 2014 AF Guidelines, class III anti-arrhythmic drugs are not recommended in patients with left ventricular hypertrophy, but in the 2020 HCM Guidelines, sotalol (STL) and dofetilide (DOF) are deemed “reasonable” for rhythm control, both based on limited data. Methods: We conducted an observational study (2001-2021) of patients with HCM who were treated with DOF or STL for AF and/or VA. Baseline characteristics and drug-related adverse events were analyzed from the electronic medical record, and rates of discontinuation and arrhythmia recurrence at 1 year and by time of chart review were compared using Kaplan Meier curves and log rank test. Results: There were 21 DOF and 52 STL HCM patients with AF, and 18 STL patients with VA. At 1 year, AF patients on DOF or STL had no significant difference in rates of AF recurrence (42.9% vs 44.2%, p=0.664) or drug discontinuation (38.1% vs 29.4%, p=0.582). Recurrence and discontinuation rates of VA on STL were comparable (Figure). Over a median follow up of 1603 days (IQR 994, 4131), there was a trend toward greater efficacy for STL with respect to less AF recurrence (p=0.085) and less frequent discontinuation (p=0.153; Figure). On univariate analysis, only NYHA class predicted AF recurrence. Reasons for discontinuation were most often for inefficacy or mild side-effects. One patient with prior alcohol septal ablation who was on STL for AF developed complete heart block followed by non-sustained torsades de pointes in the setting of a severe influenza infection and later underwent defibrillator implantation. There were no other cases of pro-arrhythmia or sudden death related to DOF. Conclusions: DOF and STL are modestly effective for the treatment of AF and VA in HCM patients, with a low rate of serious adverse events.